STEPP: Skin Toxicity Treatment in Metastatic Colorectal Cancer (mCRC) Patients Receiving Panitumumab + Irinotecan-based Therapy
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00332163
Collaborator
(none)
95
2
29
Study Details
Study Description
Brief Summary
A comparison of prophylactic treatment with reactive treatment for skin toxicity observed in patients with metastatic colorectal cancer (mCRC) who are receiving second-line irinotecan-based chemotherapy concomitantly with panitumumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
95 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open-label, Randomized Clinical Trial of Skin Toxicity Treatment in Subjects Receiving Second-line FOLFIRI or Irinotecan Only Chemotherapy Concomitantly With Panitumumab
Study Start Date
:
Apr 1, 2006
Actual Primary Completion Date
:
Jan 1, 2008
Actual Study Completion Date
:
Sep 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pre-emptive Skin Treatment Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. |
Biological: Panitumumab
Administered by intravenous infusion
Other Names:
Drug: Irinotecan
Recommended dosage regimen and administration of irinotecan was based on local standard of care, the package insert, and institutional guidelines.
Drug: FOLFIRI
Chemotherapy consisting of irinotecan with infusional 5-fluorouracil and leucovorin. Recommended dosage regimen and administration of FOLFIRI was based on local standard of care, the package insert for each product, and institutional guidelines.
Drug: Pre-emptive Skin Treatment
Pre-emptive skin treatment included a skin moisturizer (eg, Lubriderm), sunscreen (free of paraaminobenzoic acid (PABA), skin protection factor (SPF) 15 or higher, ultraviolet-A (UV-A), and UV-B protection), topical steroid (1% hydrocortisone cream) and oral antibiotic (doxycycline, 100 mg twice daily).
|
| Experimental: Reactive Skin Treatment Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
Biological: Panitumumab
Administered by intravenous infusion
Other Names:
Drug: Irinotecan
Recommended dosage regimen and administration of irinotecan was based on local standard of care, the package insert, and institutional guidelines.
Drug: FOLFIRI
Chemotherapy consisting of irinotecan with infusional 5-fluorouracil and leucovorin. Recommended dosage regimen and administration of FOLFIRI was based on local standard of care, the package insert for each product, and institutional guidelines.
Drug: Reactive Skin Treatment
Treatment was based on symptoms and severity and may have included an emollient (eg, Lubriderm, Vaseline), sunscreen (SPF ≥ 15), oral antibiotic (eg, doxycycline, ciprofloxacin, cefadroxil, amoxicillin/clavulanic acid), topical steroid (hydrocortisone cream), topical antibiotic (clindamycin), oral systemic steroid, topical medical treatment (eg, silver sulfadiazine, Silvadene), topical antihistamine or oral antihistamine (hydroxyzine)
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period [6 weeks]
Skin toxicities were assessed by the study clinician and graded according to the modified Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
Secondary Outcome Measures
- Percentage of Participants With Any Grade 2 or Higher Skin Toxicity of Any Type During the 6-week Skin Treatment Period [6 weeks]
The percentage of participants who developed at least 1 incidence of ≥ grade 2 skin toxicities of any type during the 6-week skin treatment period. Analysis of this endpoint was based on adverse event data associated with the "Skin and Subcutaneous Tissue Disorders" system organ class. Adverse events were graded according to the National Cancer Institute (NCI) CTCAE version 3.0.
- Time to First Occurrence of Specific Grade 2 or Higher Skin Toxicities of Interest [6 weeks]
The time to the first occurrence of specific grade 2 or higher skin toxicities of interest was defined as the time from the first dose of panitumumab to the date of first occurrence of specific ≥ grade 2 skin toxicities of interest. Participants who did not experience specific skin-related toxicities were censored at their last skin toxicity assessment during the skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
- Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest [6 weeks]
The percentage of participants with a most severe grade of 2, 3 or 4 specific skin toxicity of interest reported during the 6-week skin treatment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
- Time to First Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest [6 weeks]
Time to the first most severe grade ≥ 2 of all the specific skin-related toxicities of interest was defined as the time from the first dose of panitumumab to the date of the first occurrence of the most severe specific ≥ grade 2 skin toxicity of interest during the 6-week skin treatment period. Participants who did not experience any specific skin-related toxicity of grade ≥ 2 were censored at their last skin toxicity assessment during the 6-week skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
- Percentage of Participants With Panitumumab Dose Reductions Due to the Specific Skin Toxicities of Interest [6 weeks]
- Response Rate at First Scheduled Assessment [Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen.]
Tumor response was assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) at the Week 9/10 assessment visit and a corresponding CR or PR confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD; ≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.
- Best Overall Response Rate [Response was assessed at Weeks 9 and 13 and then every 8 weeks for the Q2W regimen, or at Weeks 10, 14, 22 and then every 9 weeks for the Q3W regimen until the end of treatment; median treatment duration was 13 and 17 weeks in each group respectively.]
Best overall response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) while on study. Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified RECIST criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or PD (≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.
- Rate of Disease Control at First Scheduled Assessment [Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen.]
Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Disease control rate is defined as the percentage of participants with a CR, PR or stable disease (SD) at the Week 9/10 assessment visit and a corresponding response (CR or PR) confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. SD: Neither sufficient shrinkage or increase in target lesions to qualify for PR or PD, with no progression of non-target lesions and no new lesions.
- Time to Treatment Failure [From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.]
Time-to-treatment failure is defined as the time from the date of randomization to the first date of any of the following events: discontinuation of study therapy due to any reason (except for complete response and curative surgery), progression of disease, or death due to any cause. Participants who did not discontinue, who were still alive, and who did not have disease progression were censored at the date of last contact. Time to treatment failure was analyzed using the Kaplan-Meier method.
- Time to Progression [From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.]
Time from the date of randomization to the date of observed disease progression or death due to disease progression. Participants who did not have documented disease progression were censored at the date of last tumor assessment; participants who died for reasons other than disease progression while on study were censored at the date of death. PD: At least a 20% increase in the size of target lesions, recorded since the treatment started, or at least a 25% increase in size of non-target lesions and the lesion(s) measure > 10 mm in one dimension, or the appearance of one or more new lesions. Time to progression was analyzed using the Kaplan-Meier method. This analysis excludes any data collected during follow-up for participants who began third-line treatment.
- Overall Survival [From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.]
Overall Survival is defined as the time from the date of randomization to the date of death. Participants who did not die while on study or who were lost-to-follow-up were censored at their last contact date. Overall survival was analyzed using all data regardless of whether it was collected during second- or third-line treatment.
- Progression-free Survival [From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.]
Defined as the time from the date of randomization to the first date of observed disease progression or death due to any cause (whichever comes first). Participants who were alive and had not progressed while on study were censored at the date of last progression-free tumor assessment.
- Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score [Baseline and Weeks 2, 3, 4, 5, 6 and 7]
Skin-related quality of life was assessed using the DLQI. The DLQI questionnaire asks participants to evaluate the degree that their skin condition has affected their quality of life in the last week. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); The DLQI score is calculated by summing the scores for all questions, resulting in a maximum of 30 and a minimum of 0; higher scores indicate a more impaired quality of life.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with unresectable metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization;
-
Patients who have failed first line treatment containing fluoropyrimidine and oxaliplatin based chemotherapy with or without bevacizumab for mCRC.
Exclusion Criteria:
• Prior irinotecan use for the treatment of mCRC.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00332163
Other Study ID Numbers:
- 20050184
First Posted:
Jun 1, 2006
Last Update Posted:
Feb 23, 2016
Last Verified:
Jan 1, 2016
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants enrolled at 36 sites in the United States between 17 April 2006 and 28 September 2007. |
|---|---|
| Pre-assignment Detail | Participants were stratified to receive either a FOLFIRI and panitumumab regimen or an irinotecan and panitumumab regimen based on the investigator's discretion according to local standard of care. Participants were then randomized to receive either a pre-emptive skin treatment or reactive skin treatment regimen for a 6-week skin treatment period. |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Period Title: Overall Study | ||
| STARTED | 48 | 47 |
| Received Treatment | 48 | 47 |
| COMPLETED | 48 | 47 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment | Total |
|---|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. | Total of all reporting groups |
| Overall Participants | 48 | 47 | 95 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.6
(12.7)
|
61.1
(9.9)
|
60.8
(11.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
33.3%
|
21
44.7%
|
37
38.9%
|
| Male |
32
66.7%
|
26
55.3%
|
58
61.1%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White or Caucasian |
34
70.8%
|
40
85.1%
|
74
77.9%
|
| Black or African American |
6
12.5%
|
5
10.6%
|
11
11.6%
|
| Hispanic or Latino |
5
10.4%
|
1
2.1%
|
6
6.3%
|
| Asian |
2
4.2%
|
0
0%
|
2
2.1%
|
| Native Hawaiian or other Pacific Islander |
1
2.1%
|
0
0%
|
1
1.1%
|
| Other |
0
0%
|
1
2.1%
|
1
1.1%
|
| Chemotherapy Stratification (participants) [Number] | |||
| FOLFIRI + Panitumumab Q2W |
28
58.3%
|
27
57.4%
|
55
57.9%
|
| Irinotecan + Panitumumab Q3W |
20
41.7%
|
20
42.6%
|
40
42.1%
|
Outcome Measures
| Title | Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period |
|---|---|
| Description | Skin toxicities were assessed by the study clinician and graded according to the modified Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary analysis set (all randomized participants who provided informed consent before protocol-specific procedures and who received at least 1 dose of panitumumab) |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
29
60.4%
|
62
131.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -33 | |
| Confidence Interval |
(2-Sided) 95% -51 to -14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Pre-emptive - Reactive | |
| Title | Percentage of Participants With Any Grade 2 or Higher Skin Toxicity of Any Type During the 6-week Skin Treatment Period |
|---|---|
| Description | The percentage of participants who developed at least 1 incidence of ≥ grade 2 skin toxicities of any type during the 6-week skin treatment period. Analysis of this endpoint was based on adverse event data associated with the "Skin and Subcutaneous Tissue Disorders" system organ class. Adverse events were graded according to the National Cancer Institute (NCI) CTCAE version 3.0. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
40
83.3%
|
62
131.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -22 | |
| Confidence Interval |
(2-Sided) 95% -42 to -3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Pre-emptive - Reactive | |
| Title | Time to First Occurrence of Specific Grade 2 or Higher Skin Toxicities of Interest |
|---|---|
| Description | The time to the first occurrence of specific grade 2 or higher skin toxicities of interest was defined as the time from the first dose of panitumumab to the date of first occurrence of specific ≥ grade 2 skin toxicities of interest. Participants who did not experience specific skin-related toxicities were censored at their last skin toxicity assessment during the skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [weeks] |
NA
|
2.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 0.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio estimated from a Cox Proportional Hazards regression model with an indicator for treatment (pre-emptive vs. reactive), stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest |
|---|---|
| Description | The percentage of participants with a most severe grade of 2, 3 or 4 specific skin toxicity of interest reported during the 6-week skin treatment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Grade 2 |
23
47.9%
|
40
85.1%
|
| Grade 3 |
6
12.5%
|
21
44.7%
|
| Grade 4 |
0
0%
|
0
0%
|
| Title | Time to First Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest |
|---|---|
| Description | Time to the first most severe grade ≥ 2 of all the specific skin-related toxicities of interest was defined as the time from the first dose of panitumumab to the date of the first occurrence of the most severe specific ≥ grade 2 skin toxicity of interest during the 6-week skin treatment period. Participants who did not experience any specific skin-related toxicity of grade ≥ 2 were censored at their last skin toxicity assessment during the 6-week skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [weeks] |
NA
|
2.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 0.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio estimated from a Cox Proportional Hazards regression model with an indicator for treatment (Pre-emptive vs. Reactive) stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Percentage of Participants With Panitumumab Dose Reductions Due to the Specific Skin Toxicities of Interest |
|---|---|
| Description | |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
6
12.5%
|
11
23.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -4 | |
| Confidence Interval |
(2-Sided) 95% -16 to 7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Pre-emptive - Reactive | |
| Title | Response Rate at First Scheduled Assessment |
|---|---|
| Description | Tumor response was assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) at the Week 9/10 assessment visit and a corresponding CR or PR confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD; ≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions. |
| Time Frame | Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set; participants who discontinued prematurely without a post-baseline tumor assessment or with an observed CR or PR at Week 9 or 10 that was not confirmed at Week 13/14 were considered non-responders. |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
6
12.5%
|
6
12.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -10 to 10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Pre-emptive - Reactive | |
| Title | Best Overall Response Rate |
|---|---|
| Description | Best overall response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) while on study. Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified RECIST criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or PD (≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions. |
| Time Frame | Response was assessed at Weeks 9 and 13 and then every 8 weeks for the Q2W regimen, or at Weeks 10, 14, 22 and then every 9 weeks for the Q3W regimen until the end of treatment; median treatment duration was 13 and 17 weeks in each group respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set; participants who prematurely discontinued without a post-baseline tumor assessment or with an observed CR or PR that was not confirmed were considered non-responders. |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
15
31.3%
|
11
23.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 4 | |
| Confidence Interval |
(2-Sided) 95% -9 to 17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Rate difference = Pre-emptive - Reactive | |
| Title | Rate of Disease Control at First Scheduled Assessment |
|---|---|
| Description | Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Disease control rate is defined as the percentage of participants with a CR, PR or stable disease (SD) at the Week 9/10 assessment visit and a corresponding response (CR or PR) confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. SD: Neither sufficient shrinkage or increase in target lesions to qualify for PR or PD, with no progression of non-target lesions and no new lesions. |
| Time Frame | Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set; participants who prematurely discontinued without a postbaseline tumor assessment or with an observed CR or PR at Week 9 or 10 that was not confirmed at Week 13 or 14 were considered non-responders. |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Number (95% Confidence Interval) [percentage of participants] |
63
131.3%
|
64
136.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -1 | |
| Confidence Interval |
(2-Sided) 95% -21 to 18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Rate difference = Pre-emptive - Reactive | |
| Title | Time to Treatment Failure |
|---|---|
| Description | Time-to-treatment failure is defined as the time from the date of randomization to the first date of any of the following events: discontinuation of study therapy due to any reason (except for complete response and curative surgery), progression of disease, or death due to any cause. Participants who did not discontinue, who were still alive, and who did not have disease progression were censored at the date of last contact. Time to treatment failure was analyzed using the Kaplan-Meier method. |
| Time Frame | From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [months] |
3.1
|
4.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio estimated from a Cox Proportional Hazards regression model with an indicator for treatment (Pre-emptive vs. Reactive) stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Time to Progression |
|---|---|
| Description | Time from the date of randomization to the date of observed disease progression or death due to disease progression. Participants who did not have documented disease progression were censored at the date of last tumor assessment; participants who died for reasons other than disease progression while on study were censored at the date of death. PD: At least a 20% increase in the size of target lesions, recorded since the treatment started, or at least a 25% increase in size of non-target lesions and the lesion(s) measure > 10 mm in one dimension, or the appearance of one or more new lesions. Time to progression was analyzed using the Kaplan-Meier method. This analysis excludes any data collected during follow-up for participants who began third-line treatment. |
| Time Frame | From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [months] |
4.9
|
4.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio estimated from a Cox Proportional Hazards regression model with an indicator for treatment (Pre-emptive vs. Reactive) stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Overall Survival |
|---|---|
| Description | Overall Survival is defined as the time from the date of randomization to the date of death. Participants who did not die while on study or who were lost-to-follow-up were censored at their last contact date. Overall survival was analyzed using all data regardless of whether it was collected during second- or third-line treatment. |
| Time Frame | From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [months] |
11.2
|
13.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 2.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio estimated from a Cox Proportional Hazards regression model with an indicator for treatment (Pre-emptive vs. Reactive) stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Progression-free Survival |
|---|---|
| Description | Defined as the time from the date of randomization to the first date of observed disease progression or death due to any cause (whichever comes first). Participants who were alive and had not progressed while on study were censored at the date of last progression-free tumor assessment. |
| Time Frame | From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 48 | 47 |
| Median (95% Confidence Interval) [months] |
4.7
|
4.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pre-emptive Skin Treatment, Reactive Skin Treatment |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 1.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio is estimated from a Cox Proportional Hazards regression model with an indicator for treatment (Pre-emptive vs. Reactive) stratified by chemotherapy stratum (Q2W vs Q3W). | |
| Title | Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score |
|---|---|
| Description | Skin-related quality of life was assessed using the DLQI. The DLQI questionnaire asks participants to evaluate the degree that their skin condition has affected their quality of life in the last week. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); The DLQI score is calculated by summing the scores for all questions, resulting in a maximum of 30 and a minimum of 0; higher scores indicate a more impaired quality of life. |
| Time Frame | Baseline and Weeks 2, 3, 4, 5, 6 and 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patient Reported Outcomes (PRO) Analysis Set (randomized participants who signed informed consent before protocol-specified procedures, received at least 1 dose of panitumumab, with a non-missing baseline overall DLQI score and who had at least 1 post-baseline non-missing overall DLQI score) with available data at each time point. |
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment |
|---|---|---|
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. |
| Measure Participants | 46 | 44 |
| Baseline (n=46, 44) |
0.3
(0.7)
|
0.1
(0.3)
|
| Change from Baseline to Week 2 (n=42, 41) |
0.7
(1.4)
|
1.6
(3.7)
|
| Change from Baseline to Week 3 (n=44, 42) |
1.3
(2.6)
|
4.2
(5.8)
|
| Change from Baseline to Week 4 (n=42, 42) |
1.7
(2.4)
|
3.8
(5.4)
|
| Change from Baseline to Week 5 (n=44, 42) |
1.3
(2.3)
|
2.7
(4.2)
|
| Change from Baseline to Week 6 (n=42, 38) |
1.6
(2.8)
|
2.3
(3.9)
|
| Change from Baseline to Week 7 (n=40, 40) |
2.0
(2.8)
|
2.6
(4.4)
|
Adverse Events
| Time Frame | The reporting time frame is from first dose date to 30 days since the last dose date. The median time frames for pre-emptive skin treatment and reactive skin treatment are 3.5 months and 4.7 months, respectively. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. | |||
| Arm/Group Title | Pre-emptive Skin Treatment | Reactive Skin Treatment | ||
| Arm/Group Description | Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy. | Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required. | ||
All Cause Mortality |
||||
| Pre-emptive Skin Treatment | Reactive Skin Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Pre-emptive Skin Treatment | Reactive Skin Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/48 (27.1%) | 23/47 (48.9%) | ||
| Blood and lymphatic system disorders | ||||
| FEBRILE NEUTROPENIA | 0/48 (0%) | 3/47 (6.4%) | ||
| LEUKOPENIA | 0/48 (0%) | 1/47 (2.1%) | ||
| NEUTROPENIA | 0/48 (0%) | 3/47 (6.4%) | ||
| THROMBOCYTOPENIA | 0/48 (0%) | 1/47 (2.1%) | ||
| Cardiac disorders | ||||
| ATRIAL FIBRILLATION | 0/48 (0%) | 1/47 (2.1%) | ||
| BRADYCARDIA | 0/48 (0%) | 1/47 (2.1%) | ||
| CARDIO-RESPIRATORY ARREST | 1/48 (2.1%) | 0/47 (0%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 2/48 (4.2%) | 3/47 (6.4%) | ||
| DIARRHOEA | 2/48 (4.2%) | 8/47 (17%) | ||
| GASTROINTESTINAL PERFORATION | 1/48 (2.1%) | 0/47 (0%) | ||
| ILEUS | 0/48 (0%) | 1/47 (2.1%) | ||
| NAUSEA | 2/48 (4.2%) | 2/47 (4.3%) | ||
| PROCTALGIA | 1/48 (2.1%) | 0/47 (0%) | ||
| SMALL INTESTINAL OBSTRUCTION | 0/48 (0%) | 1/47 (2.1%) | ||
| VOMITING | 3/48 (6.3%) | 4/47 (8.5%) | ||
| General disorders | ||||
| ASTHENIA | 1/48 (2.1%) | 2/47 (4.3%) | ||
| DEATH | 1/48 (2.1%) | 0/47 (0%) | ||
| FATIGUE | 1/48 (2.1%) | 0/47 (0%) | ||
| NON-CARDIAC CHEST PAIN | 0/48 (0%) | 1/47 (2.1%) | ||
| PYREXIA | 1/48 (2.1%) | 0/47 (0%) | ||
| Infections and infestations | ||||
| CENTRAL LINE INFECTION | 0/48 (0%) | 1/47 (2.1%) | ||
| CLOSTRIDIAL INFECTION | 0/48 (0%) | 1/47 (2.1%) | ||
| FUNGAL INFECTION | 0/48 (0%) | 1/47 (2.1%) | ||
| GASTROENTERITIS | 0/48 (0%) | 1/47 (2.1%) | ||
| LOCALISED INFECTION | 0/48 (0%) | 1/47 (2.1%) | ||
| SEPSIS | 0/48 (0%) | 2/47 (4.3%) | ||
| SEPTIC SHOCK | 0/48 (0%) | 1/47 (2.1%) | ||
| STAPHYLOCOCCAL ABSCESS | 1/48 (2.1%) | 0/47 (0%) | ||
| STREPTOCOCCAL ABSCESS | 1/48 (2.1%) | 0/47 (0%) | ||
| URINARY TRACT INFECTION | 0/48 (0%) | 1/47 (2.1%) | ||
| Injury, poisoning and procedural complications | ||||
| FALL | 0/48 (0%) | 1/47 (2.1%) | ||
| JOINT INJURY | 0/48 (0%) | 1/47 (2.1%) | ||
| Investigations | ||||
| WEIGHT DECREASED | 1/48 (2.1%) | 0/47 (0%) | ||
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 3/48 (6.3%) | 9/47 (19.1%) | ||
| ELECTROLYTE IMBALANCE | 0/48 (0%) | 1/47 (2.1%) | ||
| FAILURE TO THRIVE | 0/48 (0%) | 1/47 (2.1%) | ||
| HYPERKALAEMIA | 0/48 (0%) | 1/47 (2.1%) | ||
| HYPOKALAEMIA | 0/48 (0%) | 3/47 (6.4%) | ||
| HYPOMAGNESAEMIA | 0/48 (0%) | 1/47 (2.1%) | ||
| HYPONATRAEMIA | 1/48 (2.1%) | 0/47 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| MUSCULAR WEAKNESS | 0/48 (0%) | 1/47 (2.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| COLON CANCER | 1/48 (2.1%) | 1/47 (2.1%) | ||
| COLON CANCER METASTATIC | 0/48 (0%) | 1/47 (2.1%) | ||
| COLORECTAL CANCER METASTATIC | 1/48 (2.1%) | 0/47 (0%) | ||
| NEOPLASM | 1/48 (2.1%) | 0/47 (0%) | ||
| Nervous system disorders | ||||
| HEMIPLEGIA | 0/48 (0%) | 1/47 (2.1%) | ||
| SYNCOPE | 0/48 (0%) | 1/47 (2.1%) | ||
| Psychiatric disorders | ||||
| DEPRESSION | 0/48 (0%) | 1/47 (2.1%) | ||
| MENTAL STATUS CHANGES | 1/48 (2.1%) | 0/47 (0%) | ||
| Renal and urinary disorders | ||||
| RENAL FAILURE | 0/48 (0%) | 1/47 (2.1%) | ||
| RENAL FAILURE ACUTE | 0/48 (0%) | 2/47 (4.3%) | ||
| URETERIC OBSTRUCTION | 0/48 (0%) | 1/47 (2.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| DYSPNOEA | 0/48 (0%) | 1/47 (2.1%) | ||
| LUNG INFILTRATION | 1/48 (2.1%) | 0/47 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| RASH | 0/48 (0%) | 1/47 (2.1%) | ||
| Vascular disorders | ||||
| HYPERTENSION | 0/48 (0%) | 1/47 (2.1%) | ||
| VENA CAVA THROMBOSIS | 0/48 (0%) | 1/47 (2.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Pre-emptive Skin Treatment | Reactive Skin Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/48 (97.9%) | 47/47 (100%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 11/48 (22.9%) | 16/47 (34%) | ||
| NEUTROPENIA | 9/48 (18.8%) | 19/47 (40.4%) | ||
| THROMBOCYTOPENIA | 1/48 (2.1%) | 6/47 (12.8%) | ||
| Eye disorders | ||||
| CONJUNCTIVITIS | 3/48 (6.3%) | 4/47 (8.5%) | ||
| EYE IRRITATION | 1/48 (2.1%) | 3/47 (6.4%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 13/48 (27.1%) | 12/47 (25.5%) | ||
| ABDOMINAL PAIN UPPER | 3/48 (6.3%) | 7/47 (14.9%) | ||
| CONSTIPATION | 13/48 (27.1%) | 14/47 (29.8%) | ||
| DIARRHOEA | 26/48 (54.2%) | 38/47 (80.9%) | ||
| DRY MOUTH | 3/48 (6.3%) | 4/47 (8.5%) | ||
| DYSPEPSIA | 6/48 (12.5%) | 3/47 (6.4%) | ||
| FLATULENCE | 3/48 (6.3%) | 3/47 (6.4%) | ||
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/48 (2.1%) | 3/47 (6.4%) | ||
| NAUSEA | 32/48 (66.7%) | 24/47 (51.1%) | ||
| PROCTALGIA | 0/48 (0%) | 3/47 (6.4%) | ||
| STOMATITIS | 11/48 (22.9%) | 14/47 (29.8%) | ||
| VOMITING | 21/48 (43.8%) | 16/47 (34%) | ||
| General disorders | ||||
| ASTHENIA | 7/48 (14.6%) | 7/47 (14.9%) | ||
| CHILLS | 5/48 (10.4%) | 3/47 (6.4%) | ||
| FATIGUE | 28/48 (58.3%) | 27/47 (57.4%) | ||
| MUCOSAL INFLAMMATION | 11/48 (22.9%) | 11/47 (23.4%) | ||
| OEDEMA PERIPHERAL | 1/48 (2.1%) | 6/47 (12.8%) | ||
| PAIN | 5/48 (10.4%) | 1/47 (2.1%) | ||
| PYREXIA | 6/48 (12.5%) | 3/47 (6.4%) | ||
| Hepatobiliary disorders | ||||
| HYPERBILIRUBINAEMIA | 0/48 (0%) | 3/47 (6.4%) | ||
| Infections and infestations | ||||
| PARONYCHIA | 8/48 (16.7%) | 17/47 (36.2%) | ||
| RASH PUSTULAR | 13/48 (27.1%) | 19/47 (40.4%) | ||
| SKIN INFECTION | 2/48 (4.2%) | 5/47 (10.6%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 2/48 (4.2%) | 7/47 (14.9%) | ||
| URINARY TRACT INFECTION | 3/48 (6.3%) | 5/47 (10.6%) | ||
| Injury, poisoning and procedural complications | ||||
| SKIN LACERATION | 2/48 (4.2%) | 6/47 (12.8%) | ||
| Investigations | ||||
| WEIGHT DECREASED | 11/48 (22.9%) | 12/47 (25.5%) | ||
| WHITE BLOOD CELL COUNT DECREASED | 4/48 (8.3%) | 1/47 (2.1%) | ||
| Metabolism and nutrition disorders | ||||
| ANOREXIA | 14/48 (29.2%) | 11/47 (23.4%) | ||
| DECREASED APPETITE | 1/48 (2.1%) | 7/47 (14.9%) | ||
| DEHYDRATION | 5/48 (10.4%) | 13/47 (27.7%) | ||
| HYPERKALAEMIA | 0/48 (0%) | 3/47 (6.4%) | ||
| HYPOCALCAEMIA | 3/48 (6.3%) | 5/47 (10.6%) | ||
| HYPOKALAEMIA | 9/48 (18.8%) | 13/47 (27.7%) | ||
| HYPOMAGNESAEMIA | 7/48 (14.6%) | 12/47 (25.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 1/48 (2.1%) | 5/47 (10.6%) | ||
| BACK PAIN | 2/48 (4.2%) | 6/47 (12.8%) | ||
| MUSCULOSKELETAL CHEST PAIN | 1/48 (2.1%) | 4/47 (8.5%) | ||
| PAIN IN EXTREMITY | 2/48 (4.2%) | 6/47 (12.8%) | ||
| Nervous system disorders | ||||
| DIZZINESS | 5/48 (10.4%) | 5/47 (10.6%) | ||
| HEADACHE | 1/48 (2.1%) | 4/47 (8.5%) | ||
| NEUROPATHY | 1/48 (2.1%) | 4/47 (8.5%) | ||
| NEUROPATHY PERIPHERAL | 6/48 (12.5%) | 7/47 (14.9%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 2/48 (4.2%) | 7/47 (14.9%) | ||
| DEPRESSION | 3/48 (6.3%) | 7/47 (14.9%) | ||
| INSOMNIA | 6/48 (12.5%) | 10/47 (21.3%) | ||
| Renal and urinary disorders | ||||
| DYSURIA | 3/48 (6.3%) | 0/47 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 5/48 (10.4%) | 9/47 (19.1%) | ||
| DYSPHONIA | 3/48 (6.3%) | 1/47 (2.1%) | ||
| DYSPNOEA | 7/48 (14.6%) | 3/47 (6.4%) | ||
| EPISTAXIS | 3/48 (6.3%) | 5/47 (10.6%) | ||
| PHARYNGOLARYNGEAL PAIN | 2/48 (4.2%) | 4/47 (8.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ALOPECIA | 15/48 (31.3%) | 13/47 (27.7%) | ||
| DERMATITIS ACNEIFORM | 37/48 (77.1%) | 40/47 (85.1%) | ||
| DERMATITIS EXFOLIATIVE | 11/48 (22.9%) | 12/47 (25.5%) | ||
| DRY SKIN | 12/48 (25%) | 9/47 (19.1%) | ||
| ERYTHEMA | 9/48 (18.8%) | 9/47 (19.1%) | ||
| NAIL DISORDER | 7/48 (14.6%) | 10/47 (21.3%) | ||
| PRURITUS | 30/48 (62.5%) | 32/47 (68.1%) | ||
| RASH | 3/48 (6.3%) | 6/47 (12.8%) | ||
| RASH ERYTHEMATOUS | 3/48 (6.3%) | 2/47 (4.3%) | ||
| RASH PRURITIC | 19/48 (39.6%) | 20/47 (42.6%) | ||
| SKIN EXFOLIATION | 16/48 (33.3%) | 19/47 (40.4%) | ||
| SKIN FISSURES | 13/48 (27.1%) | 16/47 (34%) | ||
| SKIN ULCER | 5/48 (10.4%) | 4/47 (8.5%) | ||
| Vascular disorders | ||||
| HYPOTENSION | 2/48 (4.2%) | 4/47 (8.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00332163
Other Study ID Numbers:
- 20050184
First Posted:
Jun 1, 2006
Last Update Posted:
Feb 23, 2016
Last Verified:
Jan 1, 2016